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Optimizing ceftolozane-tazobactam dosage during continuous renal replacement therapy: some nuances

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The original article was published in Critical Care 2019 23:406

We have read the recent letter by Honore et al. [1] about our findings published in this journal regarding the influence of continuous renal replacement therapy (CRRT) on the pharmacokinetics of ceftolozane-tazobactam (C/T) [2]. In our report, we decided to administer a 3 g/iv dose every 8 h taking into account two previous studies referenced in our paper [2] and another one which showed CRRT to be an independent predictor of clinical failure (OR 4.5, 95% CI 1.18–17.39, p = 0.02) when C/T is administered at 1.5 g every 8 h [3].

As Honore et al. explain in their paper, the C/T eliminitation was assumed by hemodiafiltration and the adsorption was not assessed [1]. However, there is a misunderstanding in this letter [1], because we used a polysulphone membrane (Fresenius, Germany) instead of an acrylonitrile 69 Multiflow (AN-69-M). In contrast to highly adsorptive membranes (HAM; e.g., AN69 surface-treated, AN69-ST), the antibiotic adsorption with polysulphone ones is negligible, which facilitates antibiotic adaptation during CRRT [4].

Our data should not be extrapolated to other clinical scenarios, as noted by Honore et al. [1]. In our report, ceftolozane and tazobactam plasma concentrations remained above the minimal inhibitory concentration (MIC), for MICs of up to 8 μg/mL, but we estimated that the administration of standard doses of 1 g/0.5 g, even with polysulphone membranes, could compromise the effectiveness of C/T for not reaching adequate tazobactam concentrations. Thus, the use of HAM would represent a real risk factor of clinical failure when a C/T dose of 1.5 g every 8 h is administered, especially in multidrug-resistant infections [3]. Therefore, we agree with Honore et al. [1] that therapeutic drug monitoring (TDM) is critical when using C/T for patients receiving CRRT, especially when MICs of bacteria like multidrug-resistant (MDR) Pseudomonas aeruginosa are considered very high. However, the recommendation of continuous (over 24 h) vs extended (over 2 to 4 h) or intermittent (over 30 to 60 min) infusion of beta-lactams is still under debate [5].

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Abbreviations

AN-69-M:

Acrylonitrile 69 Multiflow

AN-69-ST:

AN69-surface treated

C/T:

Ceftolozane-tazobactam

CRRT:

Continuous renal replacement therapy

HAM:

Highly adsorptive membranes

MDR:

Multidrug-resistant

MIC:

Minimal inhibitory concentration

References

  1. 1.

    Honore PM, Mugisha A, Gutierrez LB, Redant S, Kaefer K, Gallerani A, De Bels D. Optimizing ceftolozane-tazobactam dosage during continuous renal replacement therapy: additional insights. Crit Care. 2019;23(1):406.

  2. 2.

    Aguilar G, Ferriols R, Martínez-Castro S, Ezquer C, Pastor E, Carbonell JA, Alós M, Navarro D. Optimizing ceftolozane-tazobactam dosage in critically ill patients during continuous venovenous hemodiafiltration. Crit Care. 2019;23(1):145.

  3. 3.

    Bassetti M, Castaldo N, Cattelan A, Mussini C, Righi E, Tascini C, et al. Ceftolozane/tazobactam for the treatment of serious P. aeruginosa infections: a multicenter nationwide clinical experience. Int J Antimicrob Agents. 2019 Apr;53(4):408–15.

  4. 4.

    Honore PM, Spapen HD. What a clinician should know about a renal replacement membrane? J Transl Intern Med. 2018;6:62–5.

  5. 5.

    Lee YR, Miller PD, Alzghari SK, Blanco DD, Hager JD, Kuntz KS. Continuous infusion versus intermittent bolus of beta-lactams in critically ill patients with respiratory infections: a systematic review and meta-analysis. Eur J Drug Metab Pharmacokinet. 2018;43(2):155–70.

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GA, RF, and DN designed the paper. All authors participated in drafting and reviewing the manuscript. All authors read and approved the final version of the manuscript.

Correspondence to Gerardo Aguilar.

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This reply refers to the comment available at: https://doi.org/10.1186/s13054-019-2692-2.

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Aguilar, G., Ferriols, R., Martínez-Castro, S. et al. Optimizing ceftolozane-tazobactam dosage during continuous renal replacement therapy: some nuances. Crit Care 24, 11 (2020) doi:10.1186/s13054-019-2724-y

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